PAIN®最新文献

{"title":"Trigeminal neuralgia and its comorbidities: a nationwide disease trajectory study.","authors":"Jacob Worm, Isabella Friis Jørgensen, Ólafur Birgir Davídsson, Henrik Hjalgrim, Timo Röder, Sisse Rye Ostrowski, Ole Birger Pedersen, Christian Erikstrup, Mie Topholm Bruun, Bitten Aagaard Jensen, Erik Sørensen, Henrik Ullum, Gyða Björnsdóttir, Thorgeir Thorgeirsson, Hreinn Stefánsson, Ólafur Árni Sveinsson, Kári Stefánsson, Henrik Winther Schytz, Lars Bendtsen, Søren Brunak, Thomas Folkmann Hansen, Stine Maarbjerg","doi":"10.1097/j.pain.0000000000003428","DOIUrl":"https://doi.org/10.1097/j.pain.0000000000003428","url":null,"abstract":"<p><strong>Abstract: </strong>There is a limited understanding of risk factors and comorbidities in trigeminal neuralgia, a disease characterized by paroxysms of severe unilateral facial pain and a higher incidence in women. We aim to identify temporally associated comorbidities involving trigeminal neuralgia by analyzing nationwide disease trajectories. Using data from 7.2 million unique individuals in the Danish National Patient Register between 1994 and 2018, each individual diagnosed with trigeminal neuralgia was compared with 10,000 matched controls to identify co-occurring diseases. The sequential disease associations were identified in sex-stratified disease trajectories. A Cox-regression analysis investigated whether treatment with carbamazepine or oxcarbazepine, as compared with gabapentin, pregabalin, or lamotrigine, was associated with stroke risk. Finally, we investigated the stroke polygenic risk score and its association with stroke incidence in a subset of genotyped individuals with trigeminal neuralgia. We included 7141 individuals with trigeminal neuralgia (64.2% female, mean age at diagnosis 58.7 years) and identified 18 diseases associated with subsequent trigeminal neuralgia. After diagnosis, trigeminal neuralgia was associated with 9 diseases, including ischemic stroke (relative risk 1.55). Carbamazepine or oxcarbazepine treatment increased the ischemic stroke risk (hazard ratio 1.78; 95% confidence interval 1.47-2.17); however, the polygenic risk of stroke showed no association. In the Danish population, a trigeminal neuralgia diagnosis is temporally associated with 27 diseases revealed in systematic disease trajectories. Trigeminal neuralgia itself and its first-line treatment, but not a stroke polygenic risk score, was associated with an increased risk of ischemic stroke indicating that vascular risk factors should be routinely assessed in individuals with trigeminal neuralgia.</p>","PeriodicalId":19921,"journal":{"name":"PAIN®","volume":null,"pages":null},"PeriodicalIF":5.9,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142372501","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The downside to choice: instrumental control increases conditioned nocebo hyperalgesia.","authors":"Biya Tang, Evan Livesey, Ben Colagiuri","doi":"10.1097/j.pain.0000000000003251","DOIUrl":"10.1097/j.pain.0000000000003251","url":null,"abstract":"<p><strong>Abstract: </strong>Nocebo hyperalgesia is a pervasive problem in which the treatment context triggers negative expectations that exacerbate pain. Thus, developing ethical strategies to mitigate nocebo hyperalgesia is crucial. Emerging research suggests that choice has the capacity to reduce nocebo side effects, but choice effects on nocebo hyperalgesia have not been explored. This study investigated the impact of choice on conditioned nocebo hyperalgesia using a well-established electrocutaneous pain paradigm where increases in noxious stimulation were surreptitiously paired with the activation of a sham device. In study 1, healthy volunteers (N = 104) were randomised to choice over (nocebo) treatment administration, nocebo administration without choice, or a natural history control group. Nocebo hyperalgesia was greater for those with choice than no choice, suggesting that choice increased rather than diminished nocebo hyperalgesia. Study 2 tested whether providing positive information about the benefits of choice in coping with pain could counteract heightened nocebo hyperalgesia caused by choice. A different sample of healthy adults (N = 137) were randomised to receive nocebo treatment with choice and positive choice information, choice only, or no choice. The positive choice information failed to attenuate the effect of choice on nocebo hyperalgesia. The current results suggest that, rather than decreasing nocebo hyperalgesia, treatment choice may exacerbate pain outcomes when a painful procedure is repeatedly administered. As such, using choice as a strategy to mitigate nocebo outcomes should be treated with caution.</p>","PeriodicalId":19921,"journal":{"name":"PAIN®","volume":null,"pages":null},"PeriodicalIF":5.9,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140864649","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Longitudinal examination of associations with the onset of pediatric chronic pain at different pain locations.","authors":"Lisa-Marie Rau, Clarissa Humberg, Anna Könning, Nicola Rosenthal, Lorin Stahlschmidt, Julia Wager","doi":"10.1097/j.pain.0000000000003237","DOIUrl":"10.1097/j.pain.0000000000003237","url":null,"abstract":"<p><strong>Abstract: </strong>Chronic pain is a frequent phenomenon in pediatrics. Little research explores whether there are factors that uniquely predict or accompany the onset of new chronic pain in different locations of the body. In this study, we report pediatric pain data for 3 location subsamples-headache, abdominal pain, and musculoskeletal pain-of a large secondary school sample (N = 2280). We distinguished between participants who experienced an onset of chronic pain and participants who had no chronic pain at the respective pain location within a 1-year period. We used regression and multilevel models to compare the 2 groups regarding factors previously associated with chronic pain. Our results indicate that irrespective of location, the onset of chronic pain is predicted by psychosocial factors, in particular, symptoms of depression (odds ratio [OR] = 1.13-1.17, P < 0.01) and anxiety (OR = 1.12-1.21, P < 0.05). Although the onset of headache is predicted by psychosocial factors only, the onsets of abdominal and musculoskeletal pain are additionally predicted by physiological factors such as level of physical activity. Many of the predictors were also accompanying factors. Regarding chronic abdominal pain, sleep deficiency did not predict pain onset but was a co-occurring phenomenon. Our findings underline the importance of mental health factors in the pain onset at all 3 body locations, whereas in chronic abdominal and musculoskeletal pain, physiological factors should also be considered. Measures of model fit, however, indicate that the occurrence of chronic pain is more complex and not well predicted by these factors alone.</p>","PeriodicalId":19921,"journal":{"name":"PAIN®","volume":null,"pages":null},"PeriodicalIF":5.9,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140877008","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pain reflects the informational value of nociceptive inputs.","authors":"Michel-Pierre Coll, Zoey Walden, Pierre-Alexandre Bourgoin, Veronique Taylor, Pierre Rainville, Manon Robert, Dang Khoa Nguyen, Pierre Jolicoeur, Mathieu Roy","doi":"10.1097/j.pain.0000000000003254","DOIUrl":"10.1097/j.pain.0000000000003254","url":null,"abstract":"<p><strong>Abstract: </strong>Pain perception and its modulation are fundamental to human learning and adaptive behavior. This study investigated the hypothesis that pain perception is tied to pain's learning function. Thirty-one participants performed a threat conditioning task where certain cues were associated with a possibility of receiving a painful electric shock. The cues that signaled potential pain or safety were regularly changed, requiring participants to continually establish new associations. Using computational models, we quantified participants' pain expectations and prediction errors throughout the task and assessed their relationship with pain perception and electrophysiological responses. Our findings suggest that subjective pain perception increases with prediction error, that is, when pain was unexpected. Prediction errors were also related to physiological nociceptive responses, including the amplitude of nociceptive flexion reflex and electroencephalography markers of cortical nociceptive processing (N1-P2-evoked potential and gamma-band power). In addition, higher pain expectations were related to increased late event-related potential responses and alpha/beta decreases in amplitude during cue presentation. These results further strengthen the idea of a crucial link between pain and learning and suggest that understanding the influence of learning mechanisms in pain modulation could help us understand when and why pain perception is modulated in health and disease.</p>","PeriodicalId":19921,"journal":{"name":"PAIN®","volume":null,"pages":null},"PeriodicalIF":5.9,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140877009","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Data-driven identification of distinct pain drawing patterns and their association with clinical and psychological factors: a study of 21,123 patients with spinal pain.","authors":"Natalie Hong Siu Chang, Casper Nim, Steen Harsted, James J Young, Søren O'Neill","doi":"10.1097/j.pain.0000000000003261","DOIUrl":"10.1097/j.pain.0000000000003261","url":null,"abstract":"<p><strong>Abstract: </strong>The variability in pain drawing styles and analysis methods has raised concerns about the reliability of pain drawings as a screening tool for nonpain symptoms. In this study, a data-driven approach to pain drawing analysis has been used to enhance the reliability. The aim was to identify distinct clusters of pain patterns by using latent class analysis (LCA) on 46 predefined anatomical areas of a freehand digital pain drawing. Clusters were described in the clinical domains of activity limitation, pain intensity, and psychological factors. A total of 21,123 individuals were included from 2 subgroups by primary pain complaint (low back pain (LBP) [n = 15,465]) or midback/neck pain (MBPNP) [n = 5658]). Five clusters were identified for the LBP subgroup: LBP and radiating pain (19.9%), radiating pain (25.8%), local LBP (24.8%), LBP and whole leg pain (18.7%), and widespread pain (10.8%). Four clusters were identified for the MBPNP subgroup: MBPNP bilateral posterior (19.9%), MBPNP unilateral posterior + anterior (23.6%), MBPNP unilateral posterior (45.4%), and widespread pain (11.1%). The clusters derived by LCA corresponded to common, specific, and recognizable clinical presentations. Statistically significant differences were found between these clusters in every self-reported health domain. Similarly, for both LBP and MBPNP, pain drawings involving more extensive pain areas were associated with higher activity limitation, more intense pain, and more psychological distress. This study presents a versatile data-driven approach for analyzing pain drawings to assist in managing spinal pain.</p>","PeriodicalId":19921,"journal":{"name":"PAIN®","volume":null,"pages":null},"PeriodicalIF":5.9,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11404331/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140922659","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Elucidation of neuronal activity in mouse models of temporomandibular joint injury and inflammation by in vivo GCaMP Ca2+ imaging of intact trigeminal ganglion neurons.","authors":"Hyeonwi Son, John Shannonhouse, Yan Zhang, Ruben Gomez, Felix Amarista, Daniel Perez, Edward Ellis, Man-Kyo Chung, Yu Shin Kim","doi":"10.1097/j.pain.0000000000003421","DOIUrl":"https://doi.org/10.1097/j.pain.0000000000003421","url":null,"abstract":"<p><strong>Abstract: </strong>Patients with temporomandibular disorders (TMDs) typically experience facial pain and discomfort or tenderness in the temporomandibular joint (TMJ), causing disability in daily life. Unfortunately, existing treatments for TMD are not always effective, creating a need for more advanced, mechanism-based therapies. In this study, we used in vivo GCaMP3 Ca2+ imaging of intact trigeminal ganglia (TG) to characterize functional activity of the TG neurons in vivo, specifically in mouse models of TMJ injury and inflammation. This system allows us to observe neuronal activity in intact anatomical, physiological, and clinical conditions and to assess neuronal function and response to various stimuli. We observed a significant increase in spontaneously and transiently activated neurons responding to mechanical, thermal, and chemical stimuli in the TG of mice with TMJ injection of complete Freund adjuvant or with forced mouth opening (FMO). An inhibitor of the calcitonin gene-related peptide receptor significantly attenuated FMO-induced facial hypersensitivity. In addition, we confirmed the attenuating effect of calcitonin gene-related peptide antagonist on FMO-induced sensitization by in vivo GCaMP3 Ca2+ imaging of intact TG. Our results contribute to unraveling the role and activity of TG neurons in the TMJ pain, bringing us closer to understanding the pathophysiological processes underlying TMJ pain after TMJ injury. Our study also illustrates the utility of in vivo GCaMP3 Ca2+ imaging of intact TG for studies aimed at developing more targeted and effective treatments for TMJ pain.</p>","PeriodicalId":19921,"journal":{"name":"PAIN®","volume":null,"pages":null},"PeriodicalIF":5.9,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142372500","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Patients' perspective on the chronic pain classification in the 11th revision of the International Classification of Diseases (ICD-11): results from an international web-based survey.","authors":"Beatrice Korwisi, Ginea Hay, Patrice Forget, Deirdre Ryan, Rolf-Detlef Treede, Winfried Rief, Antonia Barke","doi":"10.1097/j.pain.0000000000003248","DOIUrl":"10.1097/j.pain.0000000000003248","url":null,"abstract":"<p><strong>Abstract: </strong>The 11th revision of the International Classification of Diseases and Related Health Problems (ICD-11) aims at improving the lives of persons with the lived experience of chronic pain by providing clearly defined and clinically useful diagnoses that can reduce stigma, facilitate communication, and improve access to pain management, among others. The aim of this study was to assess the perspective of people with chronic pain on these diagnoses. An international web-based survey was distributed among persons with the lived experience of chronic pain. After having seen an information video, participants rated the diagnoses on 8 endorsement scales (eg, diagnostic fit, stigma) that ranged from -5 to +5 with 0 representing the neutral point of no expected change. Overall ratings and differences between participants with chronic primary pain (CPP) and chronic secondary pain (CSP) were analyzed. N = 690 participants were included in the data analysis. The ratings on all endorsement scales were significantly higher than the neutral point of 0. The highest ratings were obtained for \"openness\" (2.95 ± 1.93) and \"overall opinion\" (1.87 ± 1.98). Participants with CPP and CSP did not differ in their ratings; however, those with CSP indicated an improved diagnostic fit of the new diagnoses, whereas participants with CPP rated the diagnostic fit of the new diagnoses similar to the fit of their current diagnoses. These results show that persons with the lived experience of chronic pain accept and endorse the new diagnoses. This endorsement is an important indicator of the diagnoses' clinical utility and can contribute to implementation and advocacy.</p>","PeriodicalId":19921,"journal":{"name":"PAIN®","volume":null,"pages":null},"PeriodicalIF":5.9,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140867175","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The prevalence of chronic pain in children and adolescents: a systematic review update and meta-analysis.","authors":"Christine T Chambers, Justine Dol, Perri R Tutelman, Charlotte L Langley, Jennifer A Parker, Brittany T Cormier, Gary J Macfarlane, Gareth T Jones, Darlene Chapman, Nicole Proudfoot, Amy Grant, Justina Marianayagam","doi":"10.1097/j.pain.0000000000003267","DOIUrl":"10.1097/j.pain.0000000000003267","url":null,"abstract":"<p><strong>Abstract: </strong>Chronic pain, defined as persistent or recurring pain or pain lasting longer than 3 months, is a common childhood problem. The objective of this study was to conduct an updated systematic review and meta-analysis on the prevalence of chronic pain (ie, overall, headache, abdominal pain, back pain, musculoskeletal pain, multisite/general pain, and other) in children and adolescents. EMBASE, PubMed, CINAHL, and PsycINFO were searched for publications between January 1, 2009, and June 30, 2023. Studies reporting population-based estimates of chronic nondisease related pain prevalence in children or adolescents (age ≤ 19 years) were included. Two independent reviewers screened articles based on a priori protocol. One hundred nineteen studies with a total of 1,043,878 children (52.0% female, mean age 13.4 years [SD 2.4]) were included. Seventy different countries were represented, with the highest number of data points of prevalence estimates coming from Finland and Germany (n = 19 each, 4.3%). The overall prevalence of chronic pain in children and adolescents was 20.8%, with the highest prevalence for headache and musculoskeletal pain (25.7%). Overall, and for all types of pain except for back pain and musculoskeletal pain, there were significant differences in the prevalence between boys and girls, with girls having a higher prevalence of pain. There was high heterogeneity (I 2 99.9%). Overall risk of bias was low to moderate. In summary, approximately 1 in 5 children and adolescents experience chronic pain and prevalence varies by pain type; for most types, there is higher pain prevalence among girls than among boys. Findings echo and expand upon the systematic review conducted in 2011.</p>","PeriodicalId":19921,"journal":{"name":"PAIN®","volume":null,"pages":null},"PeriodicalIF":5.9,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11404345/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140922660","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Social support and the association between post-traumatic stress disorder and risk for long-term prescription opioid use.","authors":"Mark D Sullivan, Lauren Wilson, Matthew Amick, Lisa R Miller-Matero, Timothy Chrusciel, Joanne Salas, Celeste Zabel, Patrick J Lustman, Brian Ahmedani, Ryan W Carpenter, Jeffrey F Scherrer","doi":"10.1097/j.pain.0000000000003286","DOIUrl":"10.1097/j.pain.0000000000003286","url":null,"abstract":"<p><strong>Abstract: </strong>Post-traumatic stress disorder (PTSD) is common in patients with chronic pain, adversely affects chronic pain outcomes, and is associated with opioid use and adverse opioid outcomes. Social support is a robust predictor of PTSD incidence and course as well as chronic pain outcome. We determined whether the association between PTSD and persistent opioid use was modified by emotional support in a cohort of patients receiving opioids for noncancer pain. Eligible participants were ≥18 years and had completed a new period of prescription opioid use lasting 30 to 90 days. Bivariate associations between cohort characteristics and each key variable was assessed using χ 2 tests for categorical variables and t -tests for continuous variables. Interaction between PTSD and emotional support was assessed by a priori stratification on low vs high emotional support. Participants (n = 808) were 53.6 (SD ± 11.6) years of age, 69.8% female, 69.6% White, and 26.4% African American. Overall, 17.2% had probable PTSD. High emotional support was significantly ( P < 0.0001) more common among those without probable PTSD. Prescription opioid use at 6-month follow-up was significantly ( P = 0.0368) more common among patients with vs without probable PTSD. In fully adjusted models, PTSD was no longer associated with opioid use at 6-month follow-up among participants with high emotional support. Among those with lower emotional support, PTSD was significantly associated with opioid use at 6-month follow-up in unadjusted (odds ratio = 2.40; 95% confidence interval: 1.24-4.64) and adjusted models (odds ratio = 2.39; 95% confidence interval: 1.14-4.99). Results point to the hypothesis that improvement of emotional support in vulnerable patients with chronic pain and PTSD may help reduce sustained opioid use.</p>","PeriodicalId":19921,"journal":{"name":"PAIN®","volume":null,"pages":null},"PeriodicalIF":5.9,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11408094/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141248334","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"CARTp/GPR160 mediates behavioral hypersensitivities in mice through NOD2.","authors":"Rachel M Schafer, Luigino A Giancotti, John C Chrivia, Ying Li, Fatma Mufti, Thomas A Kufer, Jinsong Zhang, Timothy M Doyle, Daniela Salvemini","doi":"10.1097/j.pain.0000000000003418","DOIUrl":"10.1097/j.pain.0000000000003418","url":null,"abstract":"<p><strong>Abstract: </strong>Neuropathic pain is a debilitating chronic condition that remains difficult to treat. More efficacious and safer therapeutics are needed. A potential target for therapeutic intervention recently identified by our group is the G-protein coupled receptor 160 (GPR160) and the cocaine- and amphetamine-regulated transcript peptide (CARTp) as a ligand for GPR160. Intrathecal administration of CARTp in rodents causes GPR160-dependent behavioral hypersensitivities. However, the molecular and biochemical mechanisms underpinning GPR160/CARTp-induced behavioral hypersensitivities in the spinal cord remain poorly understood. Therefore, we performed an unbiased RNA transcriptomics screen of dorsal horn spinal cord (DH-SC) tissues harvested at the time of peak CARTp-induced hypersensitivities and identified nucleotide-binding oligomerization domain-containing protein 2 (Nod2) as a gene that is significantly upregulated. Nucleotide-binding oligomerization domain-containing protein 2 is a cytosolic pattern-recognition receptor involved in activating the immune system in response to bacterial pathogens. While NOD2 is well studied under pathogenic conditions, the role of NOD2-mediated responses in nonpathogenic settings is still not well characterized. Genetic and pharmacological approaches reveal that CARTp-induced behavioral hypersensitivities are driven by NOD2, with co-immunoprecipitation studies indicating an interaction between GPR160 and NOD2. Cocaine- and amphetamine-regulated transcript peptide-induced behavioral hypersensitivities are independent of receptor-interacting protein kinase 2 (RIPK2), a common adaptor protein to NOD2. Immunofluorescence studies found NOD2 co-expressed with endothelial cells rather than glial cells, implicating potential roles for CARTp/NOD2 signaling in these cells. While these findings are based only on studies with male mice, our results identify a novel pathway by which CARTp causes behavioral hypersensitivities in the DH-SC through NOD2 and highlights the importance of NOD2-mediated responses in nonpathogenic settings.</p>","PeriodicalId":19921,"journal":{"name":"PAIN®","volume":null,"pages":null},"PeriodicalIF":5.9,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142361897","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}